Investigating the molecular mechanism of mitochondrial tethering

研究线粒体束缚的分子机制

基本信息

批准号：
9443643
负责人：
Laura L Lackner
金额：
$ 29.64万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9443643
关键词：
Address Apoptotic Architecture Avidity Binding Biochemical Biological Biological Assay Biology Calcium Cardiolipins Cell Cycle Progression Cell Death Cell membrane Cell physiology Cells Coiled-Coil Domain Complex Core Protein Data Defect Disease Exhibits Goals Grant Homeostasis Immune response Lipid Binding Lipids Mediating Membrane Mitochondria Mitochondrial Inheritance Modeling Molecular Mothers N-terminal Neurons Organelles Outer Mitochondrial Membrane PH Domain Pattern Phospholipids Phosphorylation Play Positioning Attribute Production Protein Import Proteins Publishing Regulation Resolution Role SERPINA4 gene Shapes Site Specificity Structure System Techniques Testing Time Work Yeasts cell motility daughter cell fitness insight interdisciplinary approach interest live cell imaging mitochondrial membrane protein complex small molecule spatiotemporal

项目摘要

Project Summary We are interested in the dynamic interplay between the intracellular distribution of mitochondria and cellular function. Mitochondria are important not only for cellular energy production but also play critical roles in cell cycle progression, differentiation, immune responses, lipid and calcium homeostasis, and apoptotic cell death. These diverse roles are intimately connected to mitochondrial shape and cellular position. Thus, it is not surprising aberrant mitochondrial architecture has been implicated in an ever-increasing number of diseases. Mitochondrial shape and position depend on the integrated and regulated activities of mitochondrial dynamics, motility, and tethering. A key question is how these activities are coordinated to drive the context-specific changes in the shape and position of mitochondria required to meet cellular needs. To begin to address this question, an understanding of the molecular basis of these mitochondrial activities is essential. While mitochondrial tethering plays a critical role in mitochondrial position and function in cells from yeast to neurons, it is the least understood of the activities that shape and position mitochondria. In the aims of this grant, we will address this deficit by exploiting the strengths of the facile yeast system and our expertise in cell biological and biochemical approaches to elucidate the molecular basis, mechanism, and regulation of two tether complexes that function in the distribution and inheritance of mitochondria. Understanding fundamental mechanisms used by cells to position mitochondria will provide insight into how regulated mitochondrial tethering can be harnessed to influence mitochondrial function and overall cellular homeostasis and fitness.

项目概要我们对线粒体细胞内分布之间的动态相互作用感兴趣和细胞功能。线粒体不仅对于细胞能量产生很重要，而且对于在细胞周期进程、分化、免疫反应、脂质和钙中发挥关键作用体内平衡和细胞凋亡。这些不同的角色与线粒体形状和细胞位置。因此，线粒体异常也就不足为奇了。建筑与越来越多的疾病有关。线粒体形状和位置取决于线粒体动力学的整合和调节活动，运动性和束缚。一个关键问题是如何协调这些活动以推动线粒体形状和位置的特定变化需要满足细胞需要。为了开始解决这个问题，首先要了解这些的分子基础线粒体的活动是必不可少的。虽然线粒体束缚在线粒体在从酵母到神经元的细胞中的位置和功能，是人们了解最少的塑造和定位线粒体的活动。为了实现这笔赠款的目的，我们将解决这个问题通过利用简便酵母系统的优势和我们在细胞生物学方面的专业知识来弥补缺陷和生化方法来阐明两种疾病的分子基础、机制和调控在线粒体的分布和遗传中发挥作用的系链复合物。理解细胞用于定位线粒体的基本机制将提供关于如何定位线粒体的基本机制可以利用受调节的线粒体束缚来影响线粒体功能整体细胞稳态和健康。